Guanosine 5'-diphosphate,3'-diphosphate (ppGpp) and cyclic 3',5'-adenosine monophosphate (cAMP) act as important regulators in microbial physiology. ppGpp is an effector in bacterial stringent response elicited by amino acid- or energy source-starvation. It represses the production of under-utilized metabolites, proteins, and RNA. Its synthesis in stringent cells during amino acid starvation has been characterized as a ribosomal process. However, several important questions concerning ppGpp metabolism remain unsolved. The mechanism of ppGpp synthesis in relaxed cells (relA-) is currently unclear. Unlike Escherichia coli, two distinct ppGpp-synthetases, a ribosome-independent and a ribosome-dependent, were discovered in Bacillus brevis in our laboratory. We plan to study the interrelationship between these two synthetases and their biological functions with respect to stringent-relaxed phenomena. The major pathway of ppGpp degradation in E. coli governed by the gene spoT was characterized in our laboratory. However, the control of this system by availability of energy-source is unknown. We would like to study this control with an ATP-activated ppGpp-degrading system just developed in our laboratory. Other possible minor ppGpp degradative pathways will also be explored. Adenyl cyclase, cAMP, and cAMP-binding protein were reported in yeast, Kluyveromyces (Saccharomyces) fragilis, by our laboratory. We have now discovered that cAMP specifically inhibits the out-growth of yeast from lag-phase. The biochemical mechanism underlying this phenomenon will be studied. The possible involvement of cAMP-dependent protein kinase will be explored.